Author
Listed:
- Lin Jiang
(University of Michigan Medical School)
- Haoran Su
(University of Michigan Medical School)
- Xiaoyin Wu
(University of Michigan Medical School)
- Hong Shen
(University of Michigan Medical School)
- Min-Hyun Kim
(University of Michigan Medical School)
- Yuan Li
(University of Michigan Medical School)
- Martin G. Myers
(University of Michigan Medical School
University of Michigan Medical School)
- Chung Owyang
(University of Michigan Medical School
University of Michigan Medical School)
- Liangyou Rui
(University of Michigan Medical School
University of Michigan Medical School)
Abstract
Leptin stimulates the sympathetic nervous system (SNS), energy expenditure, and weight loss; however, the underlying molecular mechanism remains elusive. Here, we uncover Sh2b1 in leptin receptor (LepR) neurons as a critical component of a SNS/brown adipose tissue (BAT)/thermogenesis axis. LepR neuron-specific deletion of Sh2b1 abrogates leptin-stimulated sympathetic nerve activation and impairs BAT thermogenic programs, leading to reduced core body temperature and cold intolerance. The adipose SNS degenerates progressively in mutant mice after 8 weeks of age. Adult-onset ablation of Sh2b1 in the mediobasal hypothalamus also impairs the SNS/BAT/thermogenesis axis; conversely, hypothalamic overexpression of human SH2B1 has the opposite effects. Mice with either LepR neuron-specific or adult-onset, hypothalamus-specific ablation of Sh2b1 develop obesity, insulin resistance, and liver steatosis. In contrast, hypothalamic overexpression of SH2B1 protects against high fat diet-induced obesity and metabolic syndromes. Our results unravel an unrecognized LepR neuron Sh2b1/SNS/BAT/thermogenesis axis that combats obesity and metabolic disease.
Suggested Citation
Lin Jiang & Haoran Su & Xiaoyin Wu & Hong Shen & Min-Hyun Kim & Yuan Li & Martin G. Myers & Chung Owyang & Liangyou Rui, 2020.
"Leptin receptor-expressing neuron Sh2b1 supports sympathetic nervous system and protects against obesity and metabolic disease,"
Nature Communications, Nature, vol. 11(1), pages 1-13, December.
Handle:
RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15328-3
DOI: 10.1038/s41467-020-15328-3
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